Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation

Oncogene. 1991 Sep;6(9):1555-9.

Abstract

A 360 residue region encoded by the neurofibromatosis type 1 (NF1) gene shows significant homology to the catalytic domains of both mammalian GTPase-activating proteins (GAP) and yeast IRA proteins. This GAP-related domain of the NF1 gene (NF1-GRD), like the GAP and IRA protein, has been reported to mediate hydrolysis of Ras-bound GTP to GDP, resulting in inactivation of Ras protein. In the present study, we identified two different types of NF1-GRD cDNA. One (type I) is identical to the previously reported sequence, and the other (type II) contained an additional 63 bp insertion that encodes for a region of 21 amino acids in the center of the NF1-GRD molecule. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. Our observations reveal that the type I transcript is predominantly expressed in undifferentiated cells, whereas the type II transcript predominates in differentiated cells. Furthermore, the expression pattern of type I and type II NF1-GRD mRNA immediately changed in SH-SY5Y neuroblastoma cells when neuronal differentiation programs were induced by retinoic acid treatment. We propose that the differential expression of type I and type II NF1-GRD transcripts might be an 'on/off' switch that regulates the catalytic activity of the NF1 gene product, which plays an important role in the regulation of neuronal differentiation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Astrocytoma
  • Base Sequence
  • Cell Differentiation
  • Cell Line
  • Cloning, Molecular
  • DNA, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic*
  • Genes, Neurofibromatosis 1*
  • Humans
  • MAP Kinase Kinase Kinases*
  • Molecular Sequence Data
  • Neurofibromin 1
  • Neurons / cytology*
  • Oligodeoxyribonucleotides
  • Oncogene Proteins*
  • Polymerase Chain Reaction
  • Protein Conformation
  • Protein Kinases / analysis
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Proteins / genetics
  • Proto-Oncogene Proteins*
  • RNA, Messenger / genetics
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic*

Substances

  • DNA, Neoplasm
  • Neurofibromin 1
  • Oligodeoxyribonucleotides
  • Oncogene Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP3K8 protein, human

Associated data

  • GENBANK/M60915
  • GENBANK/M89914
  • GENBANK/S59631
  • GENBANK/S59635
  • GENBANK/S59842
  • GENBANK/S74923
  • GENBANK/S74924
  • GENBANK/S74925
  • GENBANK/S74926
  • GENBANK/X59065